Impaired non-homologous end joining in human primary alveolar type II cells in emphysema

Autor:	Karim Bahmed, Steven G. Kelsen, Chih-Ru Lin, Nathaniel Marchetti, Beata Kosmider, Gerard J. Criner, Roger Powell, Nathaniel Xander, Muniswamy Madesh, Sudhir Bolla, Nichole Reisdorph, Elise M. Messier, Robert J. Mason, Kelly A. Correll, Liudmila Vlasenko
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Programmed cell death DNA End-Joining Repair DNA damage Fluorescent Antibody Technique Gene Expression lcsh:Medicine medicine.disease_cause Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression medicine Animals Humans lcsh:Science Multidisciplinary business.industry Smoking lcsh:R respiratory system Pathophysiology 3. Good health Non-homologous end joining Disease Models Animal Oxidative Stress 030104 developmental biology Pulmonary Emphysema chemistry Alveolar Epithelial Cells Cancer research lcsh:Q Disease Susceptibility Reactive Oxygen Species business Biomarkers 030217 neurology & neurosurgery Oxidative stress DNA DNA Damage Protein Binding
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-018-37000-z
Popis:	Emphysema is characterized by alveolar wall destruction induced mainly by cigarette smoke. Oxidative damage of DNA may contribute to the pathophysiology of this disease. We studied the impairment of the non-homologous end joining (NHEJ) repair pathway and DNA damage in alveolar type II (ATII) cells and emphysema development. We isolated primary ATII cells from control smokers, nonsmokers, and patients with emphysema to determine DNA damage and repair. We found higher reactive oxygen species generation and DNA damage in ATII cells obtained from individuals with this disease in comparison with controls. We also observed low phosphorylation of H2AX, which activates DSBs repair signaling, in emphysema. Our results indicate the impairement of NHEJ, as detected by low XLF expression. We also analyzed the role of DJ-1, which has a cytoprotective activity. We detected DJ-1 and XLF interaction in ATII cells in emphysema, which suggests the impairment of their function. Moreover, we found that DJ-1 KO mice are more susceptible to DNA damage induced by cigarette smoke. Our results suggest that oxidative DNA damage and ineffective the DSBs repair via the impaired NHEJ may contribute to ATII cell death in emphysema.
Databáze:	OpenAIRE
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